Abstract: The principal objective of the studies detailed in this application for the NIH Director's New Innovator Award is to engineer the next generation of nanotechnology-based theranostic (diagnostic + therapeutic) technology that will facilitate non-invasive imaging, and at the same time enable targeted activation of the healing process at sites of hampered musculoskeletal repair. Bone loss, due to trauma, disease, aging, or menopause is an increasingly serious health problem, and the emerging field of bone tissue engineering seeks to develop strategies to ameliorate focal bone loss. The proposed theranostic technology harnesses the physical properties of innovative multifunctional nanomaterials (single-walled carbon nanotubes and gold nanoparticles), and an acoustic wave phenomenon induced by nanosecond electromagnetic pulses known as the photoacoustic (PA) effect. The PA-based imaging approach exploits the combined intrinsic and extrinsic photoacoustic contrast between regenerating tissues and scaffolds or transplanted cells containing nanoparticles to non-invasively image (spatially and temporally) de novo bone formation and neo- vascularization. The unique and innovative approach for photoacoustic treatment involves a biophysical stimulus to bias the differentiation of progenitor cells towards controlled osteoblastogenesis thereby enhancing the quality and quantity of bone formation in the exposed region. The investigations will provide new insights, and lay the scientific foundation for future development of an integrated imaging and therapeutic technology to monitor and treat specific skeletal pathologies. Upon complete development, this technology could be made widely available to the general public, including medically under-served populations since, as an imaging modality, it will be non-ionizing, user-friendly and cost less than other 3D imaging modalities used to monitor bone regeneration;as a therapeutic modality, it would be suitable for subjects able or unable to stand (e.g., frail elderly, spinal cord injury, confined to wheelchairs or bed-rest, experience space travel) during treatment. Public Health Relevance: Bone loss, due to trauma, disease, aging, or menopause is an increasingly serious health problem. This proposal will provide new insights, and lays the scientific foundation for future development of a theranostic (integrated therapeutic and diagnostic) technology for combined non-invasive imaging and treatment in a single setting of specific skeletal pathologies;ultimately, with this proof of principal defined, there is the possibility of development for a wider range of injuries or diseases which require targeted detection, and treatment. Upon complete development, this technology could be made widely available to the general public, including medically under-served populations since, as an imaging modality, it will be non-ionizing, userfriendly and costs less than other 3D imaging modalities used to monitor bone regeneration;as a therapeutic modality, it would be suitable for subjects able or unable to stand (e.g., frail elderly, spinal cord injury, confined to wheelchairs or bed-rest, experience space travel) during treatment for osteo-integration, fracture healing, osteoporosis and similar diseases.